This research proposal comprises the continuation of our past and present investigations concerned with granulomatous hypersensitivity in murine schistosomiasis. The main objective is to analyze the humoral and cellular immune mechanisms and their dynamic interactions occurring during the evolution and involution of the granulomatous response. The research objectives can be divided into 4 areas: 1. Analysis of the function and interaction of thymus and/or bone marrow-derived lymphocytes in the granulomatous and humoral immune resposnes to schistosome eggs and egg antigens in thymectomized, irradiated, selectively reconstituted, and in mutant athymic nude mice. 2. Identification of subpopulations of thymus-derived lymphocytes and their possible synergy in lymphokine secretion and the induction and expression of granulomatous hypersensitivity. Thymectomy, anti-thymocyte serum, cannulation, cortisone treatment and density gradient centrifugation will be employed. 3. Analysis of the mechanism of spontaneous modulation of granulomatous hypersensitivity in chronically infected mice. Inhibitory antibodies or proteins synthesized in vitro by cultured granulomas, fractionated classes of antibodies or complexes found in the circulation, and the suppressor function of lymphocytes found in desensitized or "tolerant" animals will be examined and their modulatory influences assessed. 4. The dynamic state of thymus and bone marrow-derived lymphocytes and their immune functions during the course of murine schistosomiasis will be analyzed by immunofluroescence, mitogen and antigen responsiveness, lymphokine secretion, lymphocyte circulatory patterns and antibody synthesis.